ATPase inhibitors suppress actinomycin D-induced apoptosis
in leukemia cells.
Shiono Y, Fujita Y, Oka S, Yamazaki Y.
Research Institute of Biological Resources, National Institute of Advanced
Industrial Science and Technology (AIST), Tsukuba, Ibaraki 305-8566, Japan.
BACKGROUND: Apoptosis is mediated by many kinds of enzymes such as caspases,
DNase and protein kinases. Recently, ATPase has been shown to be involved in
the apoptotic system, but its role is not fully understood. MATERIALS AND
METHODS: We investigated the effect of 8 species of ATPase inhibitors on
actinomycin D plus colcemid-induced apoptosis in human megakaryoblastic
leukemia CMK-7 cells by monitoring caspase-3 activation and DNA cleavage.
RESULTS: 2,3-Butanedione monoxime (BDM), lansoprazole, cyclopiazonic acid,
geldanamycin and radicicol suppressed the apoptosis. Among these compounds,
geldanamycin was the strongest suppressor of both caspase-3 activation and DNA
cleavage. Furthermore, Western blotting showed that radicicol suppressed the
proteolytic cleavage of procaspase-9 more strongly than BDM, lansoprazole or
cyclopiazonic acid. CONCLUSION: Since geldanamycin and radicicol are specific
inhibitors of the ATPase in HSP90, the present result implies that ATPase
activity in HSP90 plays some role in this apoptosis.
